tbuckley/cabot-search huggingface dataset:
Combining plasma and tissue next-generation sequencing provides optimal treatment selection for metastatic NSCLC: A comparative study.
Authors: Jens Samol, Lavina D. Bharwani, Puey Ling Chia, Yee hong Chia, Pritish Gehlot, Kai Xin Heah, Valerie Heong, Lavenia Kulendran, Jianri Lim, Vaishnavi Muthu, Hui Lin Teo, Elise Vong, Chong Ming Yeo, Lisa Rajah, Min-Han Tan
Journal: Journal of Clinical Oncology (2023)

e21193 Background: 64% of all NSCLC patients in the USA with targetable mutations do not receive therapy due to clinical practice gaps around biomarker identification, including guideline-recommended alterations. Similar diagnostic and access challenges are also seen in Asia, but the scope of these challenges may differ due to the different mutation profiles of NSCLC. To determine the biomarker gaps involved, we conducted a study evaluating 38 metastatic NSCLC patients who received 3 diagnostic molecular workflows, and compared all 3 results to determine potential practice gaps. This is the first study to our knowledge that evaluates 3 different diagnostic workflows for one cohort to determine relative performance. Methods: 386 newly diagnosed and pathologically confirmed patients with metastatic lung cancer were managed at our hospital over Aug 21 - Sep 22. 38 metastatic non-squamous NSCLC patients were recruited prospectively. The patients received 1 plasma NGS tests (LiquidHALLMARK, Lucence, Singapore), 1 tissue comprehensive genomic profiling (CGP) test, and a panel of single-gene molecular tests (Idylla EGFR, ALK-IHC, ROS1-FISH, PD-L1 IHC). Results: Of the 38 patients recruited for the prospective trial, liquid biopsy identified 24 actionable alterations (TAT 3-13 days), tissue NGS identified 23 actionable alterations (TAT 11-27 days) and single gene testing approach provided 17 actionable alterations (TAT variable). 6 patients did not have available tissue reports. In terms of patient numbers, liquid biopsy detected at least one G9 biomarker in 21/38 patients and tissue NGS detected at least one G9 biomarker in 22/32 patients. Combining tissue NGS and liquid biopsy provided 26/38 (68.4%) patients with targeted treatment options. Single gene testing identified at least one G9 biomarker in 16/38 (42.1%) patients. Combining tissue NGS, liquid biopsy and single gene test improved sensitivity to 73.7% (28/38 patients). Overall, an estimated 1 in 4 NSCLC patients (26.4%) would have been identified with a diagnostic strategy using combined tissue and liquid NGS, over current conventional single gene testing approaches. Conclusions: Combining tissue and liquid NGS profiling provides the best treatment selection outcomes for patients with metastatic NSCLC. Our study highlighted that a quarter of NSCLC patients in Singapore would be identified for eligible targeted treatments from adopting a nationwide NGS testing approach, ideally tissue and liquid combined, to improve cancer services.
Ethnically diverse communities and their priorities for cancer research.
Authors: Helen Winter, Fatima Ahmed, Claire Matthews, Huda Hajinur, Asha Mohamed, Shoba Dawson
Journal: Journal of Clinical Oncology (2023)

e18602 Background: Ethnic minorities in the UK tend to have poorer access to healthcare, outcomes and experiences than the majority population. They are often underrepresented in health research. Experiencing disparities compounded by the lack of involvement in research widens the inequalities gap. Methods: Targeted community engagement was implemented in the highest areas of deprivation in the South West. The project team designed a series of questions and data was collected during outreach health checks and community events by members of the team based in the community. Information was collected from individuals and from groups. Results: Forty people, from culturally and linguistically diverse communities participated. We sought help from interpreters to ensure inclusivity and information was gathered in a cultural sensitive way. This was especially important due to the sensitivity in this topic area. Demographic information was collected from those that participated. The majority were women (n = 33), men (n = 7). In terms of ethnicity the majority described themselves as Black African/Caribbean (n = 31), Arab (n = 9) and Asian (n = 3). The age range was 25 - 64 years. Twelve people identified that their actual age was different to their recorded age on the NHS system. Fourteen people had been in the UK for less than 5 years and included those identifying themselves as refugees and asylum seekers. We conducted content analysis to identify and categorise the cancer research needs identified. Key themes identified included: Easier access to screening programmes; earlier diagnosis and how to initiate onward referral; research into cancer prevention and a more holistic approach to cancer care. Only one patient had clinical trials discussed. Conclusions: Community engagement offers the opportunity to identify cancer research priorities and discuss access to cancer prevention, cancer screening programmes, therapies and clinical trials. Through actively listening to our communities and the voices seldom heard about their experience of health and cancer care, we raise awareness and provide ongoing education to health care teams, on the delivery of care that is culturally sensitive, inclusive and more tailored to an individual. Increasing the diversity of the workforce may increase representation and greater advocacy of the communities. Engaging patients more in their own cancer care and decision-making may empower them to be more involved in their health. Our findings suggest that community engagement with people from diverse communities identify areas for improvement in their cancer care and experience. This includes how we might better engage with people from diverse backgrounds on clinical trials. Addressing the priorities identified from these communities is a first step in addressing the existing inequalities. Organisations need to actively engage, listen to and empower the communities that we serve.
Quality of life during medical oncological treatment in a real-world study in a single-institution of Peru.
Authors: Patricia Rioja, Guillermo Valencia, Jhajaira M Araujo, Joseph A. Pinto, Angel Godenzi, Beatriz Neciosup, Paola Catherine Montenegro
Journal: Journal of Clinical Oncology (2023)

e18735 Background: Quality of life (QoL), defined as a state of physical, psychological and social well-being that provides satisfaction to the patient to be able to perform daily activities, has become a very important aspect in the evaluation of cancer patients. The aim of the study was to assess the QoL of cancer patients during cancer treatment. Methods: Patients undergoing intravenous systemic treatment within three months of diagnosis were identified as eligible patients. A total of 315 patients were selected of out-patient chemotherapy and hospitalization services were included between January and December 2022. QoL was measured using the EQ-5D-5L Quality of Life Questionnaire. The health personnel previously explained the questionnaire to the patient and then were applied electronically through tablets. The questionnaire had 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression; each dimension has 5 levels from no problems (level 1) to extreme problems (level 5). The Visual Analogue Scale (VAS) respondent’s self-rated health, this scale is numbered from 0 (“worst health you can imagine”) to 100 (“best health you can imagine”). Level 1 vs other levels were compared and Odds ratio, chi-square and ANOVA were used to determine associated factors. Results: A total of 315 patients were included, the mean of age was 53 (18-92) and 79.1% were women. Most patients (92%) were in good performance status (Zubrod 0-1). The proportion of patients in out-patient chemotherapy service (89%) was higher than in hospitalization service (11%). A total of 48% of patients received systemic treatment with curative intention and 52%, palliative. Chemotherapy was the most common treatment (78%). Compared to gastrointestinal and central nervous system tumors; the gynecological and thorax (GTC) (OR: 2.62; 95%CI: 1.32-5.21) and genitourinary cancers (GU) (OR: 4.57; 95%CI: 1.23-16.89) had worse mobility; GTC (OR: 3.50; 95%CI: 1.69-7.24); melanoma, breast cancer, and soft tumors (MBSC) (OR: 2.14; 95%CI: 1.12-4.11) had worse self-care; and GTC (OR: 4.00; 95%CI: 1.53-10.43) had more pain/discomfort. Besides, all patients in the out-patient chemotherapy service had worse mobility (OR: 3.15; 95%CI: 1.03-9.58) and more problems during their usual activities (OR: 3.52; 95%CI: 1.27-9.76), compared to hospitalization service. In regards to the VAS, there were differences between men and women (83.05±15.49 vs 76.08±21.13, p = 0.010 respectively) and services (78.32±19.64 vs 62.94±26.15, p = 0.011 ou-patient chemotherapy vs hospitalization, respectively). Conclusions: Our study indicates that patients with gynecologic, thoracic and genitourinary neoplasms have a poorer QoL than other diagnoses during their systemic treatments. The reasons behind this finding require further research.
The study of immune-related adverse events in a community-based centre.
Authors: Sandhya Cautha, Kevin R. Jain, Pravash Budhathoki, Tobechukwu Joseph Okobi, Tanushree Bhatt, Valentina Moirangthem, Sorab Gupta, Thanh-Ha T. Luong, Ahmad Hanif
Journal: Journal of Clinical Oncology (2023)

2642 Background: The effectiveness of immunotherapy is often hindered by the development of immune-related adverse events (IrAE). Racial minorities were under-represented in the key clinical trials that led to the approval of different immune checkpoint inhibitors (ICI). In this study, we explore the side effect profile of immune checkpoint inhibitors in our patient population that comprises almost entirely of minorities, mostly African Americans (AA) and Hispanics. We hypothesize that due to race-based differences in immune milieu of the body and disease susceptibility, the timing and severity of immunotherapy-related IrAE would be different in AA and Hispanics compared to Caucasians. This can translate into a difference in clinical outcomes as well. There have been some suggestions of a positive association of the development of IrAE with cancer survival, although the data is limited and heterogeneous. The purpose of our study is to study the frequency and severity of IrAEs in racial minority groups, compare them with previous clinical trials population, and add valuable real-world data in this underrepresented group of patients. Methods: A retrospective chart review was performed on adult patients with solid malignancies treated with any ICI between January 1, 2015 and April 30, 2022. Patients were classified according to age (greater/equal to 65y or younger), sex, race (self-identified), primary cancer, and type of immunotherapy received. Outcome data using type and severity of IrAE, time to development of IrAE, and any association with clinical outcomes was collected and analyzed using descriptive statistics as well as univariate analysis. Results: A total of 78 patients were included in the final analysis. The mean age was 68 years; 51% were males; 42.3% were Hispanics, 37% were AA, 19.7% were others, and 1% were Whites. Most common malignancy was lung cancer (65.5%). Most common ICI agent used was Pembrolizumab (n = 52) and 2 patients were treated with combination therapy using Ipilimumab and Nivolumab. 41 (52.5%) patients had IrAE of any grade while 9 (11.5%) patients experienced grade 3 side effects. None of the patients experienced grade 4 side effects. Most common IrAE of any grade was hypothyroidism (n = 14) while most common grade 3 side effect was colitis (n = 6). 31 patients were less than 65y of age. There was no significant difference in IrAE in patients less than 65 years of age vs ≥ 65 years (51.6% vs 53.1%) or grade 3 IrAE (9.6% vs 12.7%). Conclusions: In our study population consisting mostly of AA and Hispanics, the rate of IrAE of any grade as well as grade 3 or 4 IrAE with ICI therapy was comparable to what was seen in clinical trials involving these drugs. This data and its potential effects on survival outcomes need to be analyzed in prospective studies involving a larger number of patients.
Deep neural networks to predict pathological invasiveness through surgical resection images: A computer vision based prospective clinical trial in pulmonary nodules.
Authors: Henian Yao, Lintong Yao, HaiYu Zhou, Weijie Zhan, Xie Daipeng, Zekai Huang, Hongwei Lin
Journal: Journal of Clinical Oncology (2023)

3068 Background: Pathological subtypes associate with surgical strategies of pulmonary nodule, during which thoracic surgeons make surgical decision through intraoperative frozen resection diagnosis. However, frozen section is time-consuming, vague and maybe misleading due to the limited sample and subjective judgements from pathologists. This study developed a predictive deep neural network for pathological invasiveness of pulmonary nodules based on the surgical resection images of gross specimens. Methods: We prospectively collected the specimen image under standardized lighting conditions in operating theaters from patients with pulmonary nodules treated by surgery resection from June 2020 to September 2021 in Guangdong Provincial People’s Hospital. Images were assigned into training cohort, validating cohort and test cohort as 8:1:1. With data augmentation, DenseNet was applied to classify the pulmonary nodules into high-risk and low-risk group. High-risk group was defined as grade 2 and grade 3 invasive pulmonary adenocarcinoma according to IASLC, while low-risk group was defined as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and grade 1 invasive pulmonary adenocarcinoma. Predictive efficiency was evaluated through area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity, accuracy. Model performance would be compared with frozen section pathological diagnosis. Results: Among 1022 patients with pulmonary nodules enrolled, we have acquired 1080 images of the resected nodules in Guangdong Provincial People’s Hospital, with a mean age of 56 years and 39.1% of male patients. The median age of patients were 57 years in training cohort and 56 years in validating cohort, with 38.1% male patients in training cohort and 42.5% male patients in test cohort. This study included 864 images in training cohort, 108 images in validating cohort and 108 images in test cohort. Mean diameter of the nodules were 14.6mm in training cohort and 17.2mm in test cohort. In terms of predictive performance, the AUC value of ROC curves was 96.0% in training cohort and 95.0% in test cohort. In training cohort, the sensitivity of model was 97.6%, with the accuracy of 97.5% and specificity of 97.6%. In test cohort, the sensitivity of model was 97.6%, with the specificity of 90.2% and accuracy of 95.4%. Compared with frozen resection in testing cohort, our deep neural network had higher accuracy in pathological prediction (95.4% vs 88.9%). Conclusions: This study developed and validated a predictive algorithm on pathological invasiveness of pulmonary nodules through computer vision technique with highly sensitivity and specificity, which could assist the rapid evaluation for pathological invasiveness and intraoperative surgical decisions.
The risk of cerebrovascular accidents in colon cancer in the United States: A population-based national study.
Authors: Akram Alkrekshi, Abdul Rahman Al Armashi, Dina Elantably, Jiasheng Wang, Faris Hammad, Anas Al Zubaidi, Joanna M. Brell
Journal: Journal of Clinical Oncology (2023)

e15516 Background: Colon cancer is the 3rd most common cause of cancer death in the United States. However, death rates have been decreasing due to increased uptake of screening and advances in treatment; as a result, there are more than 1.5 million survivors. In addition, cancer as a risk for venous thromboembolism (VTE) is established, and the underlying mechanisms of VTE are shared with arterial thromboembolism. Yet, there is a lack of population-based data to define the risk of cerebrovascular accidents (CVA) in colon cancer. Methods: Retrospectively we analyzed data from a nationwide commercial database (Explorys, IBM) from 1999 to October 2022. It aggregates records from 26 healthcare systems across 50 states with almost 80 million patients. We identified adults over 18 years old with colon cancer and obtained data on risk factors, including sex, age over 65 years, hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), atrial fibrillation, obesity, and tobacco use. Multivariable logistic regression was used to adjust for the variables collected. All tests were two-sided, and a p-value ≤ 0.05 was considered statistically significant. Results: A population of 69,339,860 was included. Colon cancer was diagnosed in 304,650 (0.4%) and CVA in 237,290 (0.3%). Males made 45%. The colon cancer group, compared to the background population, had a higher prevalence of patients aged over 65 years (66.8% vs. 30.7%), HTN (61% vs. 21.1%), HLD (50.7% vs. 16.9%), DM (31.4% vs. 8.8%), obesity (20.7% vs. 8.0%), tobacco use (12.5% vs. 6.6%) and CVA (5% vs. 0.3%). Multivariable logistic regression of variable studies (Table). Colon cancer was significantly associated with CVA. Conclusions: Our study included over 69 million adults, making it the most extensive population-based study of the risk of CVA in colon cancer in the United States. After adjustment for most established risk factors that may confound the result, colon cancer was associated with a significantly increased risk of CVA, and it was preceded only by HTN. Colon cancer portrayed more risk than atrial fibrillation. Limitations of population-based studies are several, including inaccuracies and miscoding. Our findings suggest that colon cancer survivors and patients with stable disease on treatment may have their prognosis and quality of life jeopardized by CVA. Prospective studies are needed, and management of modifiable risk factors in collaboration with primary care is paramount. [Table: see text]
Sintilimab, SBRT and GM-CSF for metastatic NSCLC: A prospective, multicenter, phase II trial.
Authors: JianJiao Ni, Lin Wu, Qian Chu, Chengbo Han, Xinghao Ai, Xiaorong Dong, Zhengfei Zhu
Journal: Journal of Clinical Oncology (2023)

e21172 Background: PD-1/PD-L1 inhibitors have transformed the therapeutic landscape in metastatic non-small cell lung cancer (NSCLC). However, the objective response rate (ORR) remains limited in unselected population. Incorporating SBRT to PD-1/PD-L1 inhibitors may improve treatment efficacy and the anti-tumor immunity induced by SBRT may be enhanced by GM-CSF, which plays a pivotal role in dendritic cell differentiation and maturation. The current trial (NCT04106180) is the first prospective, multicenter, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), SBRT and GM-CSF in metastatic NSCLC patients without sensitizing driver mutations. Methods: Metastatic EGFR/ALK negative NSCLC pts who had failed first-line standard chemotherapy were eligible. Pts received SBRT (8 Gy*3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 3 weeks after SBRT. Sintilimab would be given continuously until disease progression, unacceptable toxicity, or up to 35 cycles. Primary end point is ORR. Secondary end points are safety, out-of-field response rate, overall survival (OS), progression free survival (PFS). The trial was designed to enroll 56 patients and if ≥17 pts evaluated had an objective response, it was regarded as positive. Results: By the time of 2022/10/30, the trial was early closed after 18 of the 51pts enrolled from 6 academic centers documented PR. The majority of pts were male, ECOG 1 and non-squamous NSCLC, having more than 5 lesions at baseline, with a median age of 62 (range, 32-74). The sites of SBRT included lung (n = 20), regional lymph node (n = 16), pleural nodule (n = 5), vertebra (n = 3), distant lymph node (n = 3), liver (n = 2) and others (n = 2). Treatment-related adverse event (TRAE) occurred in most pts and grade 3 TRAE occurred in 6 (11.8%) pts. No grade 4-5 TRAE occurred and the most common grade 3 TRAEs were ALT/AST elevation (n = 2), transient acute heart failure (recovered within 7 days) (n = 1), leucopenia/neutropenia (n = 2), pneumonitis (n = 1) and creatinine elevation (n = 1). With a median follow-up of 19.2 (range, 4.6-35.4) months, 49 pts had evaluable efficacy, with 18 PR, 15 SD and 16 PD. Median PFS and OS were 5.9 (95% CI, 3.9-9.2) and 16.2 (95% CI, 12.6-34.1) months, respectively. The results of biomarker testing will also be presented. Conclusions: Triple combination of Sintilimab, SBRT and GM-CSF is safe and shows promising efficacy in metastatic EGFR/ALK negative NSCLC. Clinical trial information: NCT04106180 .
Real world utilization and disparities in outcome in the use of novel anti-androgen agents for metastatic prostate cancer.
Authors: Samina Hirani, Ashimiyu Durojaiye, Jian He, Roy T. Sabo, Asit K. Paul
Journal: Journal of Clinical Oncology (2023)

6616 Background: Despite advances in treatment, disparities exist in prostate cancer treatment and utilization of treatment resources based on several factors including race and socioeconomic status. As evidence-based guidelines increasingly define novel androgen receptor inhibitors (ARIs) as the standard of care, it is important to understand how the utilization of ARIs impacts the outcome. In this study, we investigated the relationship between the utilization of the two most commonly used ARIs, Abiraterone and Enzalutamide, and survival among patients with metastatic prostate cancer. Methods: We conducted a retrospective analysis of patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1st, 2013 to December 31, 2017. All patients aged 18 years and above with metastatic prostate cancer were included. The objective of these study was to determine the utilization of ARIs in different groups (age, race, location, income status and marital status) and investigate the impact of these variables on the survival. Kaplan-Meir survival curves were used for the survival analysis. Patients were stratified by: who received an ARI alone or in combination vs. who did not. Log-rank tests were used to compare the stratified survival probability curves by groups. A multivariate proportional hazards model was used to compare the instantaneous risk of death in metastatic prostate cancer between patients based on selected covariates. All hypothesis tests were two-tailed with a p-value &lt; 0.05 considered statistically significant. Results: A total of 5889 patients with metastatic prostate cancer were included in the analysis. The median age was 73 years; 39% of patients received an ARI alone or in combination with other agents. Among the patients who received ARIs, 77 %, 15% and 8% were white, black and of other races, respectively. Use of ARIs were more in urban locations (98.1% vs. 1.9% at rural locations) and in patients with higher and mid-level incomes (73.0% vs. 22.7% in low-income group). While survivals were inferior in all subgroups of patients who did not receive ARIs, survivals was better in white race (vs. black and others) as well as in younger age group who received ARIs. However, in the latter group, there was no statistical difference in survival in rural vs. urban locations and low income vs. high and mid-income groups. Conclusions: Our study shows that 39% of patients with metastatic prostate cancer in the SEER Medicare population utilized an ARI.There was a significant underutilization of ARIs in non-white, rural locations and low-income subgroup. White race and younger age populations were associated with better survival irrespective of use of ARIs. Among patients who did not receive ARIs, survivals were inferior in rural (vs. urban) and low-income (vs. high and mid-income) patients, but survivals were equivalent in these subgroups who received ARIs.